The biochemical changes underlying the physiological and pathological changes occurring during cardiac hypertrophy are poorly understood. Myosin isozymic changes, primarily involving myosin heavy chain (MHC) occur in all models of cardiac hypertrophy so far studies in the rat. It has been postulated that these changes account for the changes in myosin ATPase activity and cardiac contractility in several of the pathological conditions studied in this animal model system. In order to determine some of the biochemical correlates of physiological and pathological cardiac hypertrophy we propose to study the expression of the cardiac MHC genes in normal and hypothyroid animals as well as in response to different forms of systolic and diastolic overload. For these studies we will make use of recently isolated recombinant cDNA and genomic MHC clones in combination with protein biochemical analysis to quantitate the expression of different cardiac MHC genes at the mRNA and protein level. Special attention will be paid to the nature and kinetics of the MHC switches during the development and regression of different forms of cardiac hypertrophy. Once this descriptive phase has been accomplished experiments designed to address some of the possible mechanisms involved in the gene switching at the DNA level will be undertaken. It is hoped that these studies will provide a better understanding of the biochemical parameters involved in cardiac hypertrophy and provide the basis for further analysis of one of the most common and functionally significant features of different congenital and acquired cardiopathies.